From Chronic Atrophic Gastritis to Low‐Grade Intraepithelial Neoplasia: A Proteomic Study on the Sequential Progression of Gastric Precancerous Lesions

ABSTRACT Objectives This study aimed to identify differentially expressed proteins (DEPs) in the gastric mucosa of patients with gastric precancerous lesions, establish a differential protein expression profile, and investigate the associated biological processes. Methods Quantitative proteomic analysis of gastric mucosal tissues from 60 patients—including 20 each diagnosed with chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and low‐grade intraepithelial neoplasia (LGIN)—was performed using data‐independent acquisition liquid chromatography–tandem mass spectrometry (DIA LC–MS/MS). DEPs were identified using stringent statistical criteria (|log 2 fold change [FC]| > 1.2, false discovery rate [FDR] < 0.05). Subsequent bioinformatic analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, as well as receiver operating characteristic (ROC) curve assessments. Results A total of 591 proteins were identified across the CAG, IM, and LGIN groups. Comparative analysis revealed 21 statistically significantly DEPs primarily associated with metabolic pathways, signal transduction, cytoskeletal organization, viral infection, carcinogenesis, endocytosis, and the spliceosome. Notably, Parkinson's disease protein 7 (PARK7) was consistently downregulated and exhibited differential expression across all three pathological stages. Conclusion This study delineates characteristic protein alterations in the gastric mucosa throughout the progression of gastric precancerous lesions along the CAG‐IM‐LGIN sequence. PARK7 demonstrates high diagnostic potential and may serve as a promising biomarker for monitoring disease progression in gastric precancerous conditions.